Estimation of growth hormone secretion rate: impact of kinetic assumptions intrinsic to the analytical approach

2001 ◽  
Vol 280 (1) ◽  
pp. R225-R232 ◽  
Author(s):  
Janneke G. Langendonk ◽  
Johannes D. Veldhuis ◽  
Jacobus Burggraaf ◽  
Rik C. Schoemaker ◽  
Adam F. Cohen ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Analytical Approach ◽  
Normal Weight ◽  
Secretion Rate ◽  
The Other ◽  
Upper Body ◽  
Metabolic Clearance ◽  
Obese Women ◽  
Gh Secretion ◽  
Plasma Gh

We compared four common mathematical techniques to determine daily endogenous growth hormone (GH) secretion rates from diurnal plasma GH concentration profiles in 24 women (16 upper- or lower-body obese and 8 normal-weight individuals). Two forms of deconvolution analysis and two techniques based on a priori determined GH clearance estimates were employed. Deconvolution analyses revealed significant differences in the 24-h GH secretion rate between normal-weight and upper-body obese women, whereas the other two techniques did not. Moreover, deconvolution analyses predicted that the reduction in mean plasma GH concentrations in upper-body obese women was accounted for by impaired GH secretion, whereas the other methods suggested that obesity increases GH metabolic clearance. Thus we infer that disparate conclusions concerning GH secretion can be drawn from the same primary data set. The different inferences likely reflect dissimilar kinetic assumptions and the particular limitations intrinsic to each analytical approach. Accordingly, we urge caution in the facile comparison of calculated GH secretion data in humans, especially when kinetic and secretion measurements are performed under different conditions. The most appropriate way to determine the GH secretion rate in humans must be balanced by the exact intent of the experiment and the acceptability of different assumptions in that context.

Influence of obesity and body fat distribution on growth hormone kinetics in humans

1999 ◽  
Vol 277 (5) ◽  
pp. E824-E829 ◽  
Author(s):  
Janneke G. Langendonk ◽  
A. Edo Meinders ◽  
Jacobus Burggraaf ◽  
Marijke Frölich ◽  
Corné A. M. Roelen ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Body Fat ◽  
Premenopausal Women ◽  
Human Growth ◽  
Fat Distribution ◽  
Normal Weight ◽  
Body Fat Distribution ◽  
Upper Body ◽  
Gh Secretion ◽  
Plasma Gh

We studied the kinetics of exogenous recombinant 22-kDa human growth hormone (rhGH) in premenopausal women with upper body obesity (UBO), lower body obesity (LBO), or normal body weight. A bolus of 100 mU rhGH was administered during a continuous infusion of somatostatin to suppress endogenous GH secretion. GH kinetics were investigated with noncompartmental analysis of plasma GH curves. GH peak values in response to GH infusion and plasma half-life of GH were not significantly different between normal weight and obese subjects. In contrast, GH clearance was 33% higher in LBO women and 51% higher in UBO women compared with clearance in normal weight controls. The difference in clearance between LBO and UBO was not statistically significant. Altered GH clearance characteristics contribute to low circulating GH levels in obese humans. Body fat distribution does not appear to affect GH kinetics.

Glucose homeostasis in abdominal obesity: hepatic hyperresponsiveness to growth hormone action

2004 ◽  
Vol 287 (1) ◽  
pp. E63-E68 ◽  
Author(s):  
M. M. Buijs ◽  
J. A. Romijn ◽  
J. Burggraaf ◽  
M. L. de Kam ◽  
M. Frölich ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Glucose Metabolism ◽  
Abdominal Obesity ◽  
Glucose Homeostasis ◽  
Premenopausal Women ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Normal Weight ◽  
Obese Women ◽  
Gh Secretion

It has been suggested that (abdominally) obese individuals are hypersensitive to growth hormone (GH) action. Because GH affects glucose metabolism, this may impact glucose homeostasis in abdominal obesity. Therefore, we studied the effect of GH on glucose metabolism in abdominally obese (OB) and normal-weight (NW) premenopausal women. A 1-h intravenous infusion of GH or placebo was randomly administered to six NW [body mass index (BMI) 21.1 ± 1.9 kg/m2] and six OB (BMI 35.5 ± 1.5 kg/m2) women in a crossover design. Insulin, glucagon, and GH secretion were suppressed by concomitant infusion of somatostatin. Glucose kinetics were measured using a 10-h infusion of [6,6-2H2]glucose. In both groups, similar physiological GH peaks were reached by infusion of GH. GH strongly stimulated endogenous glucose production (EGP) in both groups. The percent increase was significantly greater in OB than in NW women (29.8 ± 11.3 vs. 13.3 ± 7.4%, P = 0.014). Accordingly, GH responsiveness, defined as the maximum response of EGP per unit GH, was increased in OB vs. NW subjects (6.0 ± 2.1 vs. 2.2 ± 1.5 μmol·min−1·mU−1·l−1, P = 0.006). These results suggest that the liver is hyperresponsive to GH action in abdominally obese women. The role of the somatotropic ensemble in the control of glucose homeostasis in abdominal obesity is discussed.

Lack of growth hormone response to acute administration of dexamethasone in anorexia nervosa

1995 ◽  
Vol 132 (2) ◽  
pp. 152-158 ◽  
Author(s):  
Massimo Scacchi ◽  
Cecilia Invitti ◽  
Angela I Pincelli ◽  
Claudio Pandolfi ◽  
Antonella Dubini ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Anorexia Nervosa ◽  
Normal Subjects ◽  
High Plasma ◽  
Normal Weight ◽  
Growth Hormone Response ◽  
Acute Administration ◽  
Hormone Response ◽  
Gh Secretion ◽  
Plasma Gh

Scacchi M, Invitti C, Pincelli AI, Pandolfi C, Dubini A, Cavagnini F. Lack of growth hormone response to acute administration of dexamethasone in anorexia nervosa. Eur J Endocrinol 1995;132:152–8. ISSN 0804–4643 High plasma growth hormone (GH) levels, associated with abnormal hormone responses to provocative stimuli, point to an altered GH secretion in anorexia nervosa. The GH-releasing effect of acutely administered glucocorticoids, firmly established in normal subjects, has not been reported in these patients. In this study, acute iv administration of 4 mg of dexamethasone, compared with saline, increased plasma GH in nine normal-weight women (AUC 848.2 ± 127.95 vs 242.8 ± 55.35 μg·l−1·min−1, p < 0.05, respectively) but was ineffective in 11 anorectic patients (AUC 3271.8 ± 1407.11 vs 2780.0 ± 1162.04 μg·l−1·min−1, NS). After dexamethasone, a significant lowering of plasma cortisol was observed in normal women (AUC 25367.0 ± 3128.43 vs 47347.1 ± 4456.61 nmol·l−1·min−1, after dexamethasone and saline, respectively, p < 0.05), but not in anorectic patients (AUC 77809.3 ± 8499.92 vs 78454.9 ± 7603.62 nmol·l−1·min−1, NS). In both groups, plasma adrenocorticotrophin (ACTH) displayed a significant decrease after dexamethasone (AUC 523.6 ± 92.08 vs 874.2 ± 115.03 pmol·l−1·min−1, p < 0.05, after dexamethasone and saline, respectively, in anorectic patients and 377.5 ± 38.41 vs 1004.9 ± 200.51 pmol·l−1·min−1, p < 0.05, in controls). However, when considering the hormonal decremental areas, a significant dexamethasone-induced ACTH inhibition, compared to saline, was evidenced in normal (ΔAUC –414.4 ± 65.75 vs 222.9 ± 42.40 pmol·l−1·min−1, p < 0.05) but not in anorectic women (ΔAUC –254.2 ± 96.92 vs 2.9 ± 132.32 pmol·l−1·min−1, NS). In conclusion, compared to normal subjects, anorectic patients do not display an increase of plasma GH levels and show a lower degree of inhibition of the hypothalamic–pituitary–adrenal axis following acute iv administration of dexamethasone. This observation broadens the array of the abnormal GH responses to provocative stimuli in anorexia nervosa and supports the existence, in these patients, of a decreased hypothalamic somatostatin secretion, although the possibility of a reduced tissue sensitivity to glucocorticoids cannot be excluded. Francesco Cavagnini, 2nd Chair of Endocrinology, University of Milan, Istituto Scientifico Ospedale San Luca, Centro Auxologico Italiano, via Spagnoletto 3, 20149 Milano, Italy

Acipimox enhances spontaneous growth hormone secretion in obese women

2004 ◽  
Vol 286 (4) ◽  
pp. R693-R698 ◽  
Author(s):  
Petra Kok ◽  
Madelon M. Buijs ◽  
Simon W. Kok ◽  
Inge H. A. P. van Ierssel ◽  
Marijke Frölich ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Normal Weight ◽  
Control Group ◽  
Time Interval ◽  
Obese Women ◽  
Double Blind ◽  
Deconvolution Analysis ◽  
Gh Secretion

We hypothesized that a high circulating free fatty acid (FFA) concentration is involved in the pathogenesis of hyposomatotropism associated with obesity. To evaluate this hypothesis, 10 healthy premenopausal women (body mass index 33.8 ± 1.0 kg/m2) were studied in the follicular phase of their menstrual cycle at two occasions with a time interval of at least 8 wk, where body weight remained stable. Subjects were randomly assigned to treatment with either acipimox (an inhibitor of lipolysis, 250 mg orally 4 times daily) or placebo in a double-blind crossover design, starting 1 day before admission until the end of the blood sampling period. Blood samples were taken during 24 h with a sampling interval of 10 min for assessment of growth hormone (GH) concentrations, and GH secretion was estimated by deconvolution analysis. Identical methodology was used to study GH secretion in a historical control group of age-matched normal weight women. GH secretion was clearly blunted in obese women (total daily release 66 ± 10 vs. lean controls: 201 ± 23 mU·lVd-1·24 h-1, P = 0.005, where lVd is liter of distribution volume). Acipimox considerably enhanced total (113 ± 50 vs. 66 ± 10 mU·lVd-1·24 h-1, P = 0.02) and pulsatile GH secretion (109 ± 49 vs. 62 ± 30 mU·lVd-1·24 h-1, P = 0.02), but GH output remained lower compared with lean controls. Further analysis did not show any relationship between the effects of acipimox on GH secretion and regional body fat distribution. In conclusion, acipimox unleashes spontaneous GH secretion in obese women. It specifically enhances GH secretory burst mass. This might mean that lowering of systemic FFA concentrations by acipimox modulates neuroendocrine mechanisms that orchestrate the activity of the somatotropic ensemble.

REGULATION OF GROWTH HORMONE SECRETION IN THE OVINE FOETUS

1973 ◽  
Vol 58 (1) ◽  
pp. 89-95 ◽  
Author(s):  
A. L. C. WALLACE ◽  
B. D. STACY ◽  
G. D. THORBURN
Keyword(s):  
Growth Hormone ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
High Rate ◽  
Metabolic Clearance ◽  
Abrupt Decrease ◽  
Gh Secretion ◽  
High Concentrations ◽  
Plasma Gh ◽  
Regulation Of Growth

SUMMARY The rate of removal of immunoreactive, intravenously injected 125I-labelled sheep growth hormone (GH) was used to calculate metabolic clearance rates (MCR) in two foetal lambs at 130 days of gestation and in two 6-day-old lambs. The mean MCR calculated for the foetuses was 2·9 ml/min/kg and for the lambs 3·1 ml/min/kg. The concentration of GH in plasma sampled before injection was determined immunologically and the values were used to calculate production rates. A production rate of 924 ng GH/min was calculated for the foetuses and 85 ng GH/min for the lambs. The effect of sectioning the pituitary stalk was studied in two foetuses; after the operation there was a rapid decrease in the circulating levels of GH. Hypophysectomy in two other foetuses also caused an abrupt decrease in plasma GH concentration. It was concluded from these experiments that the exceptionally high concentrations of GH in the plasma of foetal lambs could not be attributed to impaired removal of the hormone from the circulation. The direct cause of the increased hormone concentrations was a high rate of GH secretion resulting from active stimulation of the foetal pituitary by the hypothalamus.

Secretory bursts of growth hormone secretion in the dog may be initiated by somatostatin withdrawal

1984 ◽  
Vol 62 (2) ◽  
pp. 199-207 ◽  
Author(s):  
John S. Cowan ◽  
Penney Gaul ◽  
Bruce C. Moor ◽  
Jacob Kraicer
Keyword(s):  
Growth Hormone ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Metabolic Clearance ◽  
Time Data ◽  
Basal Secretion ◽  
Gh Secretion ◽  
Plasma Gh ◽  
Secretion Rates

In 28 6-h experiments on 10 conscious resting trained male dogs, plasma growth hormone (GH) was determined at 5-min intervals by radioimmunoassay. For all experiments, the basal GH concentration in plasma was 0.80 ± 0.06 ng mL−1. In each experiment, 1–3 secretory bursts of GH occurred, raising plasma GH 2.4 to 15.3 times basal concentrations (for all 43 bursts, 6.6 ± 0.4 times the basal value). Metabolic clearance rates (MCR) and apparent distribution volumes (V) were determined, using stepwise infusions of canine GH. The MCR (3.99 ± 0.30 mL kg−1 min−1) and V (57.9 ± 5.5 mL kg−1) were used to transform the GH concentration versus time data into GH secretion rates, using a single compartment approach. Basal GH secretion rates for all 28 experiments were 3.12 ± 0.24 ng kg−1 min−1. The secretory bursts yield peak GH secretion rates of 9.4 ± 0.8 times basal secretion and these steep-sloped bursts last 25.1 ± 1.2 min. Six-hour infusions of 0.15 μg kg−1 min−1 of somatostatin (SRIF) abolished all secretory bursts but did not lower basal secretion rates. In five of seven SRIF infusion experiments in which samples were taken after the infusion ceased a secretory burst was seen in the hour following cessation of infusion (in four cases within 10 min). These secretory bursts lasted 23.0 ± 2.9 min and were similar to those seen in control experiments. Infusions of SRIF at 0.05 μg kg−1 min−1 had no effect. These results imply that during basal GH secretion, a surfeit of SRIF impinges on the somatotrophs, as extra SRIF does not further lower basal secretion. However, during secretory bursts, very little SRIF must be present, as exogenous SRIF blocks these bursts. The bursts are similar in duration to overshoots provoked in perifused dispersed rat somatotrophs by removal of an SRIF signal. It seems likely that their cause in vivo is similar. (All values are means ± SEM.)

scholarly journals The Decreased Growth Hormone Response to Growth Hormone Releasing Hormone in Obesity Is Associated to Cardiometabolic Risk Factors

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Fernando Cordido ◽  
Jesús Garcia-Buela ◽  
Susana Sangiao-Alvarellos ◽  
Teresa Martinez ◽  
Ovidio Vidal
Keyword(s):  
Insulin Resistance ◽  
Growth Hormone ◽  
Cardiovascular Risk ◽  
Ldl Cholesterol ◽  
Premenopausal Women ◽  
Fasting Insulin ◽  
Risk Markers ◽  
Obese Women ◽  
Gh Secretion ◽  
The Metabolic Syndrome

The aim of the present study was to evaluate the relationship between GHRH-induced GH secretion in obese premenopausal women and cardiovascular risk markers or insulin resistance. Premenopausal obese women, aged 35–52 years, were studied. GH secretion, IGF-I, serum cardiovascular risk markers, insulin, leptin, mid-waist and hip circumference, total body fat, and truncal fat were measured. Subjects were classified as meeting the criteria for GH deficiency (GHD) when peak GH after stimulation with GHRH was≤3 μg/L. Mean total and LDL cholesterol, fasting insulin, and HOMA-IR were all higher, in subjects who would have been classified as GH-deficient compared with GH-sufficient. Peak GH secretion after stimulation was inversely associated with fasting insulin (R=−0.650,P=.012), HOMA-IR (R=−0.846,P=.001), total cholesterol (R=−0.532,P=.034), and LDL cholesterol (R=−0.692,P=.006) and positively associated with HDL cholesterol (R=0.561,P=.037). These data strongly suggest a role for insulin resistance in the decreased GH secretion of obesity and that the blunted GH secretion of central obesity could be the pituitary expression of the metabolic syndrome.

Is there a place for urinary growth hormone measurement?

1993 ◽  
Vol 128 (3) ◽  
pp. 197-201 ◽  
Author(s):  
Maria N Moreira-Andrés ◽  
Francisco J Cañizo ◽  
Federico Hawkins
Keyword(s):  
Growth Hormone ◽  
Screening Method ◽  
Small Sample ◽  
Point Of View ◽  
Intrasubject Variability ◽  
Gh Secretion ◽  
Lack Of Information ◽  
Low Levels ◽  
Plasma Gh ◽  
Serum Gh

The evaluation of growth hormone (GH) secretion is an important problem in pediatric endocrine practice. The diagnosis of GH insufficiency is based on the finding of a "blunted" GH response to GH provocative tests or on the demonstration of a decreased endogenous secretion. From a practical point of view, these methods are uncomfortable, expensive and time consuming. Recently, very sensitive specific assays to measure human GH in urine have been developed. We present a discussion of available data on these tests in order to estimate their role in the evaluation of a short or slowly growing child. The present available assays allow measuring very low levels of GH in a small sample of untreated urine. The main limitations of urinary GH measurement are the intrasubject variability, wide normal range, overlapping results in several GH secretory states and lack of information on GH pulsatility. However, most of these limitations also apply to other tests of GH secretion. The advantage of urinary GH tests is that they provide, in an easy procedure, information on serum GH concentration. There is good correlation between urinary and serum GH concentration and several findings suggest that urinary GH excretion reflects changes in plasma GH levels during the period of urine collection. Therefore, the usefulness of urinary GH measurement is that of a simpler and cheaper screening method for assessing integrated serum GH concentration in clinical practice.

Mechanism of action of Hexarelin. I. Growth hormone-releasing activity in the rat

1996 ◽  
Vol 135 (4) ◽  
pp. 481-488 ◽  
Author(s):  
Antonio Torsello ◽  
Roberta Grilli ◽  
Marina Luoni ◽  
Margherita Guidi ◽  
Maria Cristina Ghigo ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Mechanism Of Action ◽  
Direct Action ◽  
Male Rats ◽  
Surgical Ablation ◽  
Adult Rats ◽  
Gh Secretion ◽  
Plasma Gh

Torsello A, Grilli R, Luoni M, Guidi M, Ghigo MC, Wehrenberg WB, Deghenghi R, Müller EE, Locatelli V. Mechanism of action of Hexarelin. I. Growth hormone-releasing activity in the rat. Eur J Endocrinol 1996;135:481–8. ISSN 0804–4643 We have reported Hexarelin (HEXA), an analog of growth hormone-releasing peptide 6 (GHRP-6), potently stimulates growth hormone (GH) secretion in infant and adult rats. This study was undertaken to further investigate Hexarelin's mechanisms of action. In 10-day-old pups, treatments with HEXA (80 μg/kg, b.i.d.) for 3–10 days significantly enhanced, in a time-related fashion, the GH response to an acute HEXA challenge. Qualitatively similar effects were elicited in pups passively immunized against growth hormone-releasing hormone (GHRH) from birth. In adult male rats, a 5-day pretreatment with HEXA (150 μg/kg, b.i.d.) did not enhance the effect of the acute challenge, and the same pattern was present after a 5-day pretreatment in male rats with surgical ablation of the mediobasal hypothalamus (MBH-ablated rats). In addition, in adult sham-operated rats, Hexarelin (300 μg/kg, iv) induced a GH response greater (p < 0.05) than that induced by GHRH (2 μg/kg, iv). However, in MBH-ablated rats 7 days after surgery, GHRH was significantly (p < 0.05) more effective than HEXA, and 30 days after surgery HEXA and GHRH evoked similar rises of plasma GH. Finally, the in vitro Hexarelin (10−6 mol/l) effect was transient while GHRH (10−8 mol/l) induced a longer lasting and greater GH release. Three different mechanisms, not mutually exclusive, are postulated for Hexarelin stimulation of GH secretion in vivo: a direct action on the pituitary, though of minor relevance; an indirect action that involves release of GHRH, of relevance only in adult rats; and an action through the release of a still unknown hypothalamic "factor", which in infant and adult rats elicits GH release acting sinergistically with GHRH. Antonio Torsello, Department of Pharmacology, via Vanvitelli 32, 20129 Milano, Italy

RELATIONSHIP BETWEEN LAMB BIRTH WEIGHTS AND FETAL PLASMA GROWTH HORMONE AND INSULIN CONCENTRATIONS

1986 ◽  
Vol 66 (4) ◽  
pp. 995-1001
Author(s):  
G. J. MEARS
Keyword(s):  
Growth Hormone ◽  
Fetal Growth ◽  
Plasma Insulin ◽  
Plasma Concentrations ◽  
Maternal Plasma ◽  
Metabolic Clearance ◽  
Plasma Growth Hormone ◽  
Fetal Plasma ◽  
Plasma Gh ◽  
Ovine Fetal

Plasma concentrations of growth hormone (GH) and insulin were monitored in 11 chronically cannulated ovine fetuses and their mothers during the last month of gestation to obtain information on the role that these hormones have in determining fetal growth rate. Maternal plasma GH and insulin concentrations were independent of stage of gestation and lamb birth weights. Fetal plasma insulin concentrations were episodic in nature, independent of stage of gestation, and tended to be higher in fetuses that were heavier at birth. Fetal plasma GH concentrations were only slightly episodic in nature, were tenfold higher than maternal levels at 116–124 d gestation and increased by approximately another 25% prior to parturition. Fetal plasma GH concentrations were negtively correlated with lamb birth weights. In twin preparations, fetal plasma GH concentrations were significantly lower in the twin that was heaviest at birth. The lower GH concentrations found in faster growing fetuses are suggestive of a more rapid metabolic clearance of GH by the tissues of these animals. The results indicate that circulating fetal GH and, possibly, insulin are involved in determining the rate of ovine-fetal growth. Key words: Ovine birth weights, fetal GH, fetal insulin, fetal growth

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